基于网络药理学探讨补脾胃泻阴火升阳汤治疗胃食管反流病的作用机制及实验验证  

Discussion on mechanism and experimental validation of Bupiwei Xieyinhuo Shengyang Prescription in treatment of gastroesophageal reflux disease based on network pharmacology

作　　者：梁雅琳 黄美祯 张云燕[2] 黄茂光 黎丽群 罗贞艺 蒙华莹 谢胜[2] Liang Yalin;Huang Meizhen;Zhang Yunyan;Huang Maoguang;Li Liqun;Luo Zhenyi;Meng Huaying;Xie Sheng(Graduate School of Guangxi University of Chinese Medicine,Nanning 530001,China;Spleen and Stomach Department,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530001,China)

机构地区：[1]广西中医药大学研究生院,南宁530001 [2]广西中医药大学第一附属医院脾胃科,南宁530001

出　　处：《国际中医中药杂志》2023年第3期315-322,共8页International Journal of Traditional Chinese Medicine

基　　金：广西自然科学基金项目(2021GXNSFBA196055);广西研究生教育创新计划资助项目(YCXJ2021066)。

摘　　要：目的基于网络药理学和分子对接技术研究补脾胃泻阴火升阳汤干预胃食管反流病的作用机制。方法通过TCMSP筛选补脾胃泻阴火升阳汤主要活性成分和靶点信息,采用GeneCards、OMIM、TTD、PharmGKB数据库确定胃食管反流病相关的靶点,取活性成分作用靶点和疾病靶点交集,通过STRING数据库构建PPI网络,并基于Cytoscape CytoNCA插件提取核心靶点进行分析。利用Metascape进行GO功能富集和KEGG通路富集分析,通过Cytoscape 3.7.2构建“成分-靶点-信号通路”网络,运用Autodock进行分子对接验证。采用动物实验进行验证,选取SPF级SD雄性大鼠,采用经食管支架植入术建立胃食管反流病大鼠模型,补脾胃泻阴火升阳汤干预14 d后,检测各组大鼠血清TNF-α、环氧化酶(COX-2)水平。结果共筛选出补脾胃泻阴火升阳汤的有效成分215个,其作用于胃食管反流病的主要靶点有TNF、IL6、CASP3、TP53、PTGS2等,主要集中于癌症通路、AGE-RAGE信号通路、钙信号通路、NF-κB信号通路等。分子对接结果显示,补脾胃泻阴火升阳汤关键活性成分与核心靶点的结合潜能和活性较好。经实验验证,与模型组比较,补脾胃泻阴火升阳汤组大鼠血清TNF-α、COX-2水平降低(P<0.01)。结论补脾胃泻阴火升阳汤可通过调节TNF、IL6、CASP3、TP53、PTGS2等核心靶点调控NF-κB信号通路、钙信号通路等,发挥治疗胃食管反流病的作用。Objective To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease(GERD)based on network pharmacology and molecular docking technology.Methods The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database,and targets were identified by GeneCards,OMIM,TTD and PharmGKB databases.The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING.Cytoscape CytoNCA plug-in was used to extract core targets for analysis.GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape.Cytoscape 3.7.2 was used to construct the"component-target-signal pathway"network,and Autodock was used to complete molecular docking verification.Animal experiments were further used for verification.SPF SD male rats were selected and GERD model was established by esophageal stent implantation.After 14 days of intervention,serum TNF-αand COX-2 levels of rats in each group were detected for verification.Results A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription.The main targets of GERD were TNF,IL6,CASP3,TP53 and PTGS2,which mainly focused on cancer pathway,AGE-RAGE signaling pathway,calcium signaling pathway and NF-κB signaling pathway.The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better.Compared with the model group,Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-αand COX-2(P<0.01).Conclusions By regulating TNF,IL6,CASP3,TP53,PTGS2 and other core targets,Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway,calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.

关 键 词：胃食管反流 补脾胃泻阴火升阳汤 网络药理学 分子对接模拟 实验验证 

分 类 号：R285[医药卫生—中药学]